The organizational principles that distinguish the human brain from other species have been a long-standing enigma in neuroscience. Focusing on the uniquely evolved human cortical layers 2 and 3, we computationally reconstruct the cortical architecture for mice and humans. We show that human pyramidal cells form highly complex networks, demonstrated by the increased number and simplex dimension compared to mice.
View Article and Find Full Text PDFHumans exhibit unique cognitive abilities within the animal kingdom, but the neural mechanisms driving these advanced capabilities remain poorly understood. Human cortical neurons differ from those of other species, such as rodents, in both their morphological and physiological characteristics. Could the distinct properties of human cortical neurons help explain the superior cognitive capabilities of humans? Understanding this relationship requires a metric to quantify how neuronal properties contribute to the functional complexity of single neurons, yet no such standardized measure currently exists.
View Article and Find Full Text PDFEffectively addressing ethical issues in precision medicine research in Africa requires a holistic social contract that integrates biomedical knowledge with local cultural values and Indigenous knowledge systems. Drawing on African epistemologies such as ubuntu and ujamaa and on our collective experiences in genomics and big data research for sickle cell disease, hearing impairment, and fragile X syndrome and the project Public Understanding of Big Data in Genomics Medicine in Africa, we envision a transformative shift in health research data governance in Africa that could help create a sense of shared responsibility between all stakeholders in genomics and data-driven health research in Africa. This shift includes proposing a social contract for genomics and data science in health research that is grounded in African communitarianism such as solidarity, shared decision-making, and reciprocity.
View Article and Find Full Text PDFNeurons in the cerebral cortex receive thousands of synaptic inputs per second from thousands of presynaptic neurons. How the dendritic location of inputs, their timing, strength, and presynaptic origin, in conjunction with complex dendritic physiology, impact the transformation of synaptic input into action potential (AP) output remains generally unknown for in vivo conditions. Here, we introduce a computational approach to reveal which properties of the input causally underlie AP output, and how this neuronal input-output computation is influenced by the morphology and biophysical properties of the dendrites.
View Article and Find Full Text PDFHippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though the human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical properties of human Cornu Amonis subfield 1 (CA1) pyramidal neurons can explain observed rhythms, we map the morpho-electric properties of individual CA1 pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery.
View Article and Find Full Text PDFBackground: Substance use trends are complex; they often rapidly evolve and necessitate an intersectional approach in research, service, and policy making. Current and emerging digital tools related to substance use are promising but also create a range of challenges and opportunities.
Objective: This paper reports on a backcasting exercise aimed at the development of a roadmap that identifies values, challenges, facilitators, and milestones to achieve optimal use of digital tools in the substance use field by 2030.
Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1.
View Article and Find Full Text PDFFast-spiking interneurons (FSINs) provide fast inhibition that synchronizes neuronal activity and is critical for cognitive function. Fast synchronization frequencies are evolutionary conserved in the expanded human neocortex despite larger neuron-to-neuron distances that challenge fast input-output transfer functions of FSINs. Here, we test in human neurons from neurosurgery tissue, which mechanistic specializations of human FSINs explain their fast-signaling properties in human cortex.
View Article and Find Full Text PDFHuman cortical pyramidal neurons are large, have extensive dendritic trees, and yet have unexpectedly fast input-output properties: Rapid subthreshold synaptic membrane potential changes are reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties of voltage-gated sodium (Na) and potassium (K) currents in human pyramidal neurons can explain their fast input-output properties. Human Na and K currents exhibited more depolarized voltage dependence, slower inactivation, and faster recovery from inactivation compared with their mouse counterparts.
View Article and Find Full Text PDFFront Synaptic Neurosci
September 2023
Information transfer between principal neurons in neocortex occurs through (glutamatergic) synaptic transmission. In this focussed review, we provide a detailed overview on the strength of synaptic neurotransmission between pairs of excitatory neurons in human and laboratory animals with a specific focus on data obtained using patch clamp electrophysiology. We reach two major conclusions: (1) the synaptic strength, measured as unitary excitatory postsynaptic potential (or uEPSP), is remarkably consistent across species, cortical regions, layers and/or cell-types (median 0.
View Article and Find Full Text PDFGWAS have identified numerous genes associated with human cognition but their cell type expression profiles in the human brain are unknown. These genes overlap with human accelerated regions (HARs) implicated in human brain evolution and might act on the same biological processes. Here, we investigated whether these gene sets are expressed in adult human cortical neurons, and how their expression relates to neuronal function and structure.
View Article and Find Full Text PDFWe recently showed that variants in explained Hearing Impairment (HI) in 34.1% ( = 15/44) of multiplex families in Senegal. The present study aimed to use community-based nationwide recruitment to determine the etiologies and the clinical profiles of childhood HI in Senegal.
View Article and Find Full Text PDFTo this date, there is little to no interprofessional collaboration between professionals in general and occupational health care in the Netherlands. Where earlier initiatives for improvement focused on general practitioners (GPs) and occupational physicians (OPs), we examine the role that professionals working under task delegation of GPs and OPs can play in addressing problems on multiple life domains as well as in interprofessional collaboration. We conducted three focus group interviews with 7 assistant practitioners (APs) in general practice, 11 practice nurses (PNs) in general practice and 8 APs in occupational health practice.
View Article and Find Full Text PDFThis study aimed to gain an understanding of the challenges faced by people with hearing impairment (HI) in Cameroon, their understanding of the causes of HI, and how challenges could be remedied to improve the quality of life of persons with HI. Semi-structured one-on-one in-depth interviews and observation of participant behaviour when answering questions were used to collect data from 10 HI professionals (healthcare workers and educationists), and 10 persons affected by HI (including caregivers). The results show that the different groups associate the causes of HI to genetics, environmental factors, and a spiritual curse.
View Article and Find Full Text PDFHuman cognitive abilities are generally thought to arise from cortical expansion over the course of human brain evolution. In addition to increased neuron numbers, this cortical expansion might be driven by adaptations in the properties of single neurons and their local circuits. We review recent findings on the distinct structural, functional, and transcriptomic features of human cortical neurons and their organization in cortical microstructure.
View Article and Find Full Text PDFWe have previously reported and variants in two families from Cameroon and Ghana, segregating non-syndromic hearing impairment (NSHI). In this study, biological assays were performed to further functionally investigate the pathogenicity of [c.224T>C; p.
View Article and Find Full Text PDFSynaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic transmission between pyramidal neurons in layers 2 and 3 using neurosurgically resected human middle temporal gyrus (MTG, Brodmann area 21), which is part of the distributed language circuitry.
View Article and Find Full Text PDFThis study aimed to investigate GJB2 (MIM: 121011) and GJB6 (MIM: 604418) variants associated with familial non-syndromic hearing impairment (HI) in Senegal. We investigated a total of 129 affected and 143 unaffected individuals from 44 multiplex families by segregating autosomal recessive non-syndromic HI, 9 sporadic HI cases of putative genetic origin, and 148 control individuals without personal or family history of HI. The DNA samples were screened for GJB2 coding-region variants and GJB6-D3S1830 deletions.
View Article and Find Full Text PDFPrimary sensory areas constitute crucial nodes during perceptual decision making. However, it remains unclear to what extent they mainly constitute a feedforward processing step, or rather are continuously involved in a recurrent network together with higher-order areas. We found that the temporal window in which primary visual cortex is required for the detection of identical visual stimuli was extended when task demands were increased via an additional sensory modality that had to be monitored.
View Article and Find Full Text PDFEthnopharmacological Relevance: Eight indigenous medicinal plants which are used traditionally for the treatment of tuberculosis (TB), malaria, and associated symptoms, were selected for this study.
Aim Of Study: The aim of this study was to evaluate the antiplasmodial and antimycobacterial activities of the organic and aqueous crude extracts of different plant parts, by comparing the activities of subfractions (lead-like enhanced [LLE] extracts and methanol fractions) prepared from the bioactive crude extracts.
Materials & Methods: Crude aqueous and organic extracts were prepared for 25 different plant parts obtained from eight plant species.
The neurons in the cerebral cortex are not randomly interconnected. This specificity in wiring can result from synapse formation mechanisms that connect neurons, depending on their electrical activity and genetically defined identity. Here, we report that the morphological properties of the neurons provide an additional prominent source by which wiring specificity emerges in cortical networks.
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